Splenic lymphocytes from scalded and nonscalded rats were studied for their proliferative response to phytohemagglutinin, and to allogeneic cells in a one-way mixed lymphocyte culture (MLC). A significant suppression of the proliferation of lymphocytes in both these assays was observed as early as 4 days postinjury as measured by the [3H]thymidine uptake studies. The lymphocyte response to PHA returned to normal levels by Day 21 postinjury, whereas the MLC responses continued to be suppressed. The MLC responses between nonburned and burned animals could be restored by the addition of a lymphokine-rich culture supernatant obtained from concanavalin A-activated lymphocytes from normal nonburned rats, as well as by the addition of purified human interleukin 2 (IL-2) and rat interleukin 2. However, the addition of purified human interleukin 1 and human interferon gamma (Hu-IFN-gamma) did not bring about a significant change in the proliferation of burned rat spleen cells in MLC. Cells from burned rats were also tested for the development of suppressive activity by adding splenic lymphocytes from 2-week postburn rats to an ongoing one-way MLC. The addition of lymphocytes from burned rats resulted in significant suppression (81%) of MLC responses among normal nonburned rats. The data suggest that the development of suppressor cells following burn injury along with a defect in production and/or uptake of IL-2 may be partly responsible for immune suppression following burn injury. Since the proliferative response of lymphocytes from thermally injured rats is suppressed in a similar fashion as that found in thermally injured patients, the rat appears to be a good model for the study of kinetics of immune suppression following burn injury.